The major objective of this research project is to explore problems relating to selective disruption of the complex sequence and chronology of microchemical events comprising maturation of the rat hippocampal formation (Ammon's Horn and dentate gyrus). Methods of quantitative histochemistry will be employed, combining detailed histologic observations with serial frozen section sampling and microchemical assays of the adult structure, in conjunction with similar assessment of sample homogenates and laminar assays at various stages of postnatal life. As in previous studies of developing rat and human isocortex, cerebrosides will serve as a quantitative index of myelinogenesis; DNA combined with differential cell counts will enumerate changes in the population of neural cells; RNA and protein per cell will serve as indices of cytoplasmic volume and ribosomal organelles; and ganglioside sialic acid and Na-K ATP'ase activity will reflect axodendritic arborization. Cell acquisition in development will be measured using tritiated thymidine uptake and synaptogenesis will be assessed in part using choline acetylase and glutamic acid decarboxylase activities. The massive concentration of corticosteroid receptors reported in the hippocampal formation has encouraged us to pursue the "perinatal corticosteroid syndrome," previously associated with perturbations of brain chemistry, morphology, and behavior. The goal will be to describe stages of hippocampus and dentate maturation during which a specific insult during early postnatal life may produce quantitative decrements in the maturation of neural membranes and to further specify this area's potential for recovery following such events (plasticity). We will correlate acquisition of behavior thought to be dependent on hippocampal function (spontaneous alternation) with neurochemical maturation in both normal and steroid-injected animals. We also anticipate that by subjecting postmortem specimens of the human hippocampal formation to systematic microchemical and anatomical analyses, we can contribute to our understanding of disorders associated with behavioral aberrations or focal epileptic discharge.